Molecular imaging has the potential to detect disease progression or therapeutic effectiveness earlier than most conventional methods in the fields of oncology, neurology and cardiology. Of the several promising molecular imaging technologies having been developed such as optical imaging, MRI, SPECT and PET, PET is of particular interest for drug development because of its high sensitivity and ability to provide quantitative and kinetic data.
For example positron emitting isotopes include carbon, iodine, nitrogen, and oxygen. These isotopes can replace their non-radioactive counterparts in target compounds to produce tracers that function biologically and are chemically identical to the original molecules for PET imaging. Among these isotopes 18F is the most convenient labelling isotope due to its relatively long half life (110 min) which permits the preparation of diagnostic tracers and subsequent study of biochemical processes. In addition, its low β+ energy (634 keV) is also advantageous.
The nucleophilic aromatic and aliphatic [18F]-fluoro-fluorination reaction is of great importance for [18F]-fluoro-labelled radiopharmaceuticals which are used as in vivo imaging agents targeting and visualizing diseases, e.g. solid tumours or diseases of brain. A very important technical goal in using [18F]-fluoro-labelled radiopharmaceuticals is the quick preparation and administration of the radioactive compound due to the fact that the 18F isotopes have a short half-life of about only 110 minutes.
Monoamine Oxidases (MAO, EC, 1.4.3.4) is a distinct class of amine oxidases. MAO is present in two forms: MAO A and MAO B (Med. Res. Rev. 1984, 4, 323-358). Crystal structures of MAO A and MAO B complexed by ligands have been reported (J. Med. Chem. 2004, 47, 1767-1774 and Proc. Nat. Acad. Sci. USA, 2005, 102, 12684-12689).
Search of inhibitors that are selective for both isozyme have been actively performed (e.g. J. Med. Chem. 2004, 47, 1767-1774 and Proc. Nat. Acad. Sci. USA, 2005, 102, 12684-12689). Deprenyl (1) (Biochem Pharmacol. 1972, 5, 393-408) and clorgyline (2) are potent inhibitor of mono amine oxidase inducing irreversible inhibition of the enzymes. The L-isomer of deprenyl (3) is a more potent inhibitor than the D-isomer.

Neuroprotective and other pharmaceutical effects have also been described for inhibitors (Nature Reviews Neuroscience, 2006, 295, 295-309, Br. J. Pharmacol., 2006, 147, 5287-5296). MAO B inhibitors are for example used to increase DOPA levels in CNS (Progr. Drug Res. 1992, 38, 171-297) and they have been used in clinical trials for the treatment of Alzheimer's disease based on the fact that an increased level of MAO B is involved in astrocytes associated with Alzheimer plaques (Neuroscience, 1994, 62, 15-30).
Fluorinated MAO inhibitors have been synthesized and biochemically evaluated (review: Kirk et al. in press). F-18 and C-11 labeled MAO inhibitors have been studied in vivo (Journal of the Neurological Science, (2007), 255, 17-22; review: Methods 2002, 27, 263-277). F-18 labeled deprenyl and deprenyl analogues 4-5 have also been reported (int. J. Radiat. Appl. instrument. Part A, Applied Radiat isotopes, 1991, 42, 121, J. Med. Chem. 1990, 33, 2015-2019 and Nucl. Med. Biol. 1990, 26, 111-116, respectively).

It would be desirable to have new F-18 labeled compounds and methods available to image diseases which go along with increased level of MAO receptor, especially to have imaging agents and methods available which are easy to realize and which are able to image certain levels of astrocyte activation. This task is solved with the invention shown in the diagram of FIG. 16:                The present invention provides novel compounds of Formulae Ia and Ib. If these compounds of formulae Ia and Ib are not 18F-labelled or 19F-labelled, but instead contain an appropriate leaving group, they are starting materials for the synthesis of 18F-labelled or 19F-labelled compounds of formulae Ia and Ib. 19F-labelled compounds of formulae Ia and Ib are standard reference compounds (as identification tool and for quality check) of the synthesis towards 18F-labelled compounds of formulae Ia and Ib. In the following compounds of formulae Ia and Ib which contain an appropriate leaving group and do not contain 18F or 19F, are also referred to as “precursor compounds having formula Ia or Ib”. Moreover, those compounds of formula Ia and Ib that contain 19F instead of an appropriate leaving group are also referred to as “19F standard reference compounds having formula Ia or Ib”. Moreover, those compounds of formulae Ia and Ib which contain 18F and which do not contain an appropriate leaving group are also referred to as “18F-labelled compounds of formulae Ia or Ib”.        The invention further provides a method of imaging diseases, the method comprising introducing into a patient a detectable quantity of a 18F-labeled compound of Formulae Ia or Ib or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.        The invention provides also 18F-labelled or 19F-labelled compounds of Formula Ia and Ib for use as medicament.        The present invention also provides diagnostic compositions comprising a radiolabeled compounds preferably 18F-labelled compounds of formulae Ia and Ib, and a pharmaceutically acceptable carrier or diluent.        Another aspect of the invention is directed to the use of compounds of formulae Ia and Ib for the manufacture of a medicament, in particular of 18F- or 19-F-labelled compounds of formulae Ia or Ib.        The invention also provides a process to synthesize 18F-labelled compounds of formulae Ia and Ib from precursor compounds having formulae Ia or Ib.        The invention also provides a process to synthesize 19F-labelled compounds of formulae Ia and Ib from precursor compounds having formulae Ia or Ib.        The invention also provides a process to synthesize 18F-labelled compounds of formulae Ia or Ib by reacting compounds of Formula IV with compounds of Formula VI. Compounds of formulae IV can be generated by 18F- or 19F-fluorinating a compound of formula V.        The invention also provides a kit for preparing a radiopharmaceutical preparation, said kit comprising a sealed vial containing a predetermined quantity of                    a precursor compound having formula Ia or Ib, or            compounds of Formula V and VI.                        The present invention also provides a kit for imaging diseases. More specifically the compounds of this invention are useful for the imaging of CNS diseases including but not limited to inflammatory and autoimmune, allergic, infectious and toxin-triggered and ischemia-triggered diseases, pharmacologically triggered inflammation with pathophysiological relevance, neuroinflammatory, neurodegenerative diseases. In another embodiment the compounds of this invention are useful for the imaging of tissue, in particular tumors. Examples of inflammatory and autoimmune diseases are chronic inflammatory intestinal diseases (inflammatory bowel diseases, Crohn's disease, ulcerative colitis), arthritis, atheroma, atherosclerosis, inflammatory cardiomyopathy, pemphigus, asthma, multiple sclerosis, diabetes, type I insulin-dependent diabetes mellitus, rheumatoid arthritis, lupus diseases and other collagenoses, Graves' disease, Hashimoto's disease, “graft-versus-host disease” and transplant rejections. Examples of allergic, infectious and toxin-triggered and ischemia-triggered diseases are: sarcoidosis, asthma, hypersensitive pneumonitis, sepsis, septic shock, endotoxin shock, toxic shock syndrome, toxic liver failure, ARDS (acute respiratory distress syndrome), eclampsia, cachexia, acute viral infections (e.g., mononucleosis, fulminant hepatitis), and post-reperfusion organ damage. An example of a pharmacologically triggered inflammation with pathophysiological relevance is the “first dose response” after administration of anti-T-cell antibodies such as OKT3. An example of systemic inflammation reactions of an origin that is as yet unclear is eclampsia. Examples of neurodegenerative and neuroinflammatory diseases that are associated with a astrocyte activation/MAO regulation are dementia, AIDS dementia, amyotrophic lateral sclerosis, encephalitis, neuropathic pain, Creutzfeldt-Jakob disease, Down's syndrome, diffuse Lewy body disease, Huntington's disease, leukoencephalopathy, encephalopathies, septic encephalopathy, hepatic encephalopathy, multiple sclerosis, Parkinson's disease, Pick's disease, Alzheimer's disease, frontotemporal dementia, hippocampal sclerosis, neurocysticercosis, epilepsy, stroke, ischemia, brain tumors, depression, schizophrenia, drug abuse. The invention, therefore, also relates to the use of imaging compounds for diagnosing these diseases as well as for stratification of therapy and therapy monitoring.        In a preferred embodiment compounds of this invention are useful for the imaging of multiple sclerosis, Alzheimer's disease, frontotemporal dementia, dementia with Levy bodies, leukoencephalopathy, epilepsy, neuropathic pain, amyotrophic lateral sclerosis, Parkinson's Disease, encephalopathies, brain tumors, depression, drug abuse, chronic inflammatory intestinal diseases, atheroma, atherosclerosis, arthritis, rheumatoid arthritis, pharmacologically triggered inflammation, systemic inflammation of unclear origin.        In a more preferred embodiment compounds of this invention are useful for the imaging of multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's Disease, leukoencephalopathy, encephalopathies, epilepsy, brain tumors, drug abuse, chronic inflammatory intestinal diseases, atheroma, rheumatoid arthritis, pharmacologically triggered inflammation and systemic inflammation of unclear origin.        